This invention relates to a transportable organ preservation system and more particularly to a preservation system which substantially increases the time enroute during which the organ can be maintained viable for successful implantation into a human recipient. A chilled oxygenated nutrient solution is pumped through the vascular bed of the organ after excision of the organ from the donor and during transport.
The surgical transplantation of organs has been successfully performed since 1960 owing to the improvement of surgical techniques, the introduction of by-pass circulation and the development of drugs that suppress immune rejection of the donor organ. At the present time, the donor organ is harvested under sterile conditions, cooled to about 4xc2x0 C. and placed in a plastic bag submerged in a buffered salt solution containing nutrients, and finally transplanted into the recipient. The solution is not oxygenated and is not perfused through the organ blood vessels.
The lack of donor organ availability, particularly hearts, lungs, and livers, is a limiting factor for the number of organ transplants that can be performed. At the present time, less than 25% of patients who require a heart transplant receive a new heart, and less than 10% of patients who require a lung transplant receive one. A major consideration is the length of time that a donor organ will remain viable after it is harvested until the transplant surgery is completed. For hearts, this interval is about four hours. The donor heart must be harvested, transported to the recipient, and the transplant surgery completed within this time limit. Thus, donor hearts can be used only if they are harvested at a site close to the location where the transplant surgery will take place.
It has long been known that organs will survive ex vivo for a longer time if they are cooled to 4xc2x0 C. and actively perfused through their vascular beds with a buffered salt solution containing nutrients, and that ex vivo survival of an isolated organ can be further extended if the solution is oxygenated. Several factors play a role in the prolonged survival. At 4xc2x0 C. the metabolism is greatly reduced, lowering the requirements for nutrients and oxygen, and the production of lactic acid and other toxic end products of metabolism are also greatly reduced. Circulation of the perfusion fluid replenishes the oxygen and nutrients available to the tissue, and removes the lactic acid and other toxic metabolites. The buffered solution maintains the pH and tonic strength of the tissue close to physiological.
Perfusion that allows the transport of a harvested organ from a site removed from the location where the transplant surgery will be carried out requires the use of a light weight portable device that operates under sterile conditions for pumping the cold buffered nutrient salt solution through the organ blood vessels, and in which the organ also can be transported from the site of harvesting to the site of transplantation. In order for one person to carry the entire assembly without assistance, and to transport it in an auto or airplane, it should be compact, sturdy and light weight. The system for loading the perfusion fluid should be simple and allow minimal spillage. There must be a means for oxygenating the perfusion fluid. The device requires a pump with a variably adjustable pumping rate, which pumps at a steady rate once adjusted. Sterility must be maintained. To be completely portable, the device should contain a source of oxygen, an energy source to operate the pump, and should be housed in an insulated water tight container that can be loaded with ice. An entirely satisfactory device is not currently available.
The use of a light weight, cooled, self-contained perfusion device would have a number of beneficial consequences. (1) The organs would be in better physiological condition at the time of transplantation. (2) Prolonging the survival time of donor organs will enlarge the pool of available organs by allowing organs to be harvested at a distance from the site of the transplant surgery in spite of a longer transport time. (3) It would allow more time for testing to rule out infection of the donor, for example with AIDS, hepatitis-C, herpes, or other viral or bacterial diseases. (4) The pressure on transplant surgeons to complete the transplant procedure within a short time frame would be eased. Transplant surgeons are often faced with unexpected surgical complications that prolong the time of surgery. (5) Better preservation of the integrity of the heart and the endothelium of the coronary arteries at the time of transplantation may also lessen the incidence and severity of post-transplantation coronary artery disease.
On Oct. 12, 1999 the assignee of the present invention was granted U.S. Pat. No. 5,965,433 for a portable organ profusion/oxygenation module which employed mechanically linked dual pumps and mechanically actuated flow control for pulsatile cycling of oxygenated perfusate.
The aforementioned patent contains an excellent description of the state of the art in the mid-nineties and the problems associated with transport systems for human organs. The patent also outlines the many advantages obtained by the ability to extend the transport time from approximately 4 to 24 hours.
Human organ transplantation is plagued by limitations due to insufficient time to transport an organ while maintaining its viability and by an inadequate donor pool. The present invention will significantly diminish the problem of limited transport time by providing an apparatus which will extend the transport time to up to 48 hours. This increased time will inherently increase the size of the donor pool and will allow for extensive disease testing and matching.
The present invention will also greatly reduce damage to the organ being transported and will allow organs from post-mortem donors to be used. Today, organs are only harvested from donors who are brain-dead but whose organs have never ceased to function.
Currently, an organ is transported by putting the organ in a plastic bag of storage fluid, put on ice inside a cooler. In 4 hours, 12% of the transported organs xe2x80x9cdiexe2x80x9d or become unusable, and all the organs are degraded.
A particular advantage of the transport system of the present invention is that it is easily loaded and unloaded by double-gloved surgical personnel and that the fittings require minimal dexterity to assemble and disassemble.
Another advantage of the present invention is that it does not use the flexible permeable membrane of the prior art which due to their constant flexing are subject to fatigue stresses and rupture with catastrophic results.
For the thirty-year history of organ transplantation surgery, maintaining the quality and viability of the organ has been an enormous challenge. The current method of transport, called topical hypothermia (chilling the organ in a cooler), leaves 12% of organs unusable because of their deteriorated physiological condition. Thousands of people die each year while on an ever-expanding waiting list. The need is great for a truly portable device that nurtures and oxygenates the organ throughout the entire ex-vivo transport.
Currently, when hearts, lungs, liver and certain other organs are harvested from a donor, medical teams have about 4 hours to transplant the harvested organ into the recipient. Damage to the organ at the cellular level occurs even during this short period.
Hypothermic, oxygenated perfusion devices are known in the art and have proven successful in maintaining viability of a human heart for 24 hours ex vivo in laboratory settings. While different devices are available for laboratory use under constant supervision, none are truly independently functioning and portable. For example, Gardetto et al., U.S. Pat. No. 5,965,433 describes an oxygen driven dual pump system with a claimed operating capacity of 24 hours using a single a 250 liter oxygen bottle. The intent of this device was to provide a user-friendly device that would be xe2x80x9chands offxe2x80x9d after the organ was placed in the unit. Four major problems were evident. (1) The unit contains no bubble trap and removing bubbles is difficult and time consuming. (2) The lubricant in the pumps dries out after 10 or fewer hours of operation and the pumps stop. (3) At lower atmospheric pressure such as in an aircraft in flight, the pump cycles rapidly due to the reduced resistance to pumping, risking the development of edema in the perfused organ; and (4) Two bottles of oxygen failed to produce more than 16 hours of steady operation.
Doerig U.S. Pat. No. 3,914,954 describes an electrically driven apparatus in which the perfusate is exposed to the atmosphere, breaking the sterility barrier. It must be operated upright, consumes oxygen at high rates, and is heavy. The requirement for electric power and the necessity for a portable source of electric power severely limit the portability of this unit.
O""Dell et al., U.S. Pat. No. 5,362,622, U.S. Pat. No. 5,385,821, and O""Dell U.S. Pat. No. 5,356,771 describe an organ perfusion system using a fluidic logic device or a gas pressure driven ventilator to cyclically deliver gas to a sealed chamber connected to the top of the organ canister. Cyclical delivery of gas under pressure to the upper sealed chamber serves to displace a semi-permeable membrane mounted between the gas chamber and the organ canister. Cyclical membrane displacement acts to transduce the gas pressure into fluid displacement on the opposite side, providing flow of the perfusing solution.
The membrane is chosen for its permeability to gas but not to water. This permits oxygen to flow through the membrane to oxygenate the fluid and vent carbon dioxide from the fluid. The intent of such devices is to provide a system that uses no electricity, uses low gas pressure to achieve perfusate flow, has few moving parts, provides oxygenation of the fluid, can be operated in a non-upright position, isolates the organ and perfusate from the atmosphere, is of compact size and low weight to be portable.
While these systems may work in experimental settings, they fail to meet criteria claimed by the developers. For example, the amount of oxygen necessary to cycle the membrane is very large. When calculated over a 24 hour period, it would require 4 large tanks of oxygen to assure continuous operation. This amount of oxygen fails to meet the definition of portable. The pressure and volume of oxygen required to cycle the membrane is sufficient to cause tearing of the membrane or displacing it from its margins. Either of these occurrences would be catastrophic to the organ. The manner in which fluid is cycled into the organ chamber attempts to perfuse both within and around the organ, providing freshly oxygenated fluid to infiltrate and surround the organ. This procedure is without physiological basis since normally, oxygenation is achieved by oxygen diffusion outward from the organ""s vascular bed.
All of these devices use a permeable membrane permeable to gas but not to water so that oxygen or other gas mixtures can be driven through the membrane into the perfusate and can vent CO2, produced by the organ, from the perfusate.
The successful use of permeable membranes that are subjected to repetitive variations in pressure over long periods of time depends upon the membrane having elastomeric properties to withstand such repeated flexing without tearing or rupturing. Gas permeable membranes are not built to possess such elastomeric properties.
The present invention provides a method and apparatus which allows one pressurized two liter xe2x80x9cCxe2x80x9d cylinder that contains 255 liters of oxygen at standard temperature and pressure to supply up to 34 hours of perfusion time and uses a simple electric pump driven by a storage battery to circulate the perfusion fluid through the organ being transported.
The device of the present invention is devoid of flexible membranes and instead uses flexible permeable tubing to oxygenate the perfusion fluid while the CO2 produced by the organ diffuses out of the perfusion fluid.
The vessel containing the organ to be transported is held at 4xc2x0 C. (39xc2x0 F.) by coolant blocks.
All components are designed to use injection molding as the manufacturing method.